THE CONSTITUENTS OF DIPHTHERIA TOXIN 505 



. mens of poison. In one it may amount to about one-fifth of the toxin 

 portion, in another I have seen equal parts of toxon and toxin. Dreyer 

 and Madsen in fact have recently described a poison which contained 

 three times as much toxon as toxin. According to our present ex- 

 periences, therefore, the amount of toxon calculated on the toxin can 

 vary from per cent to 300 per cent. Hence I find it impossible to 

 assume that we are dealing with neutralization phenomena such as 

 are observed with ammonia and boric acid, for such neutralizations 

 would show at least some agreement. 



This still left undecided whether the toxon is a primary bacillary 

 secretion or a secondary modification of the toxin. A study of the 

 development of one poison finally gave me the clue to this. This was 

 poison V, whose constitution has been described in the Deutsche 

 med. Wochenschrift 1898. It will be recalled that this poison pos- 

 sessed the following limits in the second phase: 



L = 0.125; L t = 0.26; L. D. = 0.003. 



During the course of three weeks Geheimrath Donitz made con- 

 tinuous determinations of L and L 1 ", using very uniform animal 

 material. The protocol of this experiment is reproduced in full 

 because the precision of the methods will thereby also be exhibited 

 (see table on page 506) . 



From the table we see that in the course of three weeks L has 

 increased from 0.15 to 0.20. After this an insignificant increase 

 brought this to 0.21; from then on L remained constant. During 

 this time the LA dose (0.26) had suffered no change whatever, for on 

 the 16th of July a mixture of 0.25 poison + 1 I. E. killed in six days 

 and 0.275 -f 1 I. E. in three days. L t , which according to our defi- 

 nition is the mixture that will just kill on the fifth day, must have 

 been about midway between these two values, a little over 0.26. 

 This agrees very well with the value obtained in the beginning. To 

 repeat, during the course of this stage L t has remained constant, 

 but L has increased considerably (from 0.125 to 0.21). 



This fact is easily explained. The toxin portion has remained 

 absolutely unchanged in" its end zone, as can at once be seen from 

 the constancy of the Lt dose. On the other hand in the toxon por- 

 tion, which is expressed by the difference between L t and L , 80 

 toxon equivalents out of 100 have apparently disappeared. This 

 eliminates the possibility of a transformation of toxin into toxon, 

 for if that assumption were correct one would expect that on allow- 



